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Beta-glycosphingolipids-mediated lipid raft alteration is associated with redistribution of NKT cells and increased intrahepatic CD8+ T lymphocyte trapping.

Abstract
The aim of this study was to determine the effect of beta-glycosphingolipids on intra-hepatic natural killer T (NKT) lymphocyte regulatory function and on lymphocyte trapping via alteration of cell membrane lipid rafts. Immune-mediated colitis was induced by intracolonic instillation of trinitrobenzene sulfonic acid. Mice were treated with beta-lactosylceramide (LC), beta-glucosylceramide (GC), beta-galactosylceramide, ceramide, or a combination of both GC and LC (IGL), or solvent alone. Lipid rafts were investigated by fluorescence-activated cell sorting analysis of ganglioside-GM1 and fluorescence microscopy of structure. Administration of beta-glycosphingolipids resulted in an increased intrahepatic/peripheral NKT ratio, increased intrahepatic CD8+ lymphocyte trapping, decreased serum interferon-gamma (IFN-gamma) levels and decreased serum IFN-gamma/interleukin-10 ratio. Administration of GC, LC, or IGL significantly altered the levels of GM1, a key marker of lipid rafts, on NKT regulatory lymphocytes. The immune modulatory effect of beta-glycosphingolipids was associated with increased survival and significant alleviation of colitis as determined by improvement in both the macroscopic and microscopic scores. In conclusion, administration of beta-glycosphingolipids increased NKT regulatory lymphocyte redistribution and intrahepatic CD8(+) T lymphocyte trapping, resulting in alleviation of immune-mediated colitis. The effects of these naturally occurring compounds were associated with modification of the T lymphocyte lipid raft structure, which is a site for immune modulation.
AuthorsGadi Lalazar, Ami Ben Ya'acov, Noa Eliakim-Raz, Dan M Livovsky, Orit Pappo, Sarah Preston, Lidya Zolotarov, Yaron Ilan
JournalJournal of lipid research (J Lipid Res) Vol. 49 Issue 9 Pg. 1884-93 (Sep 2008) ISSN: 0022-2275 [Print] United States
PMID18480029 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cytokines
  • Glycosphingolipids
  • Trinitrobenzenesulfonic Acid
Topics
  • Animals
  • CD4-CD8 Ratio
  • CD8-Positive T-Lymphocytes (immunology)
  • Colitis (chemically induced, drug therapy, immunology, pathology)
  • Cytokines (blood)
  • Glycosphingolipids (physiology, therapeutic use)
  • Killer Cells, Natural (immunology)
  • Liver (cytology)
  • Male
  • Membrane Microdomains (drug effects, metabolism)
  • Mice
  • Mice, Inbred C57BL
  • Spleen (cytology)
  • T-Lymphocytes (physiology)
  • Trinitrobenzenesulfonic Acid

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